Unstable urinary bladder contractions induced by volume provocation in subjects with detrusor hyper-reflexia secondary to spinal injuries above T12. MedDRA version: 8.1 Level: LLT Classification code 10012547 Term: Detrusor hyperreflexia
Conditions
Interventions
Product Name: PSD506
Product Code: PSD506
Pharmaceutical Form: Capsule, soft
Current Sponsor code: PSD506
Other descriptive name: R032-0
Sponsors
Plethora Solutions Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, aged 18 years or over 2. Spinal lesion above T12, which has been stable for at least 6 months prior to screening 3. Detrusor hyper- reflexia secondary to spinal injury(mid-thoracic or cervical level) present for at least 12 months 4. If female, must either be surgically sterile or post-menopausal for the past year confirmed by a negative hormone panel (luteinizing hormone [LH], follicle stimulating hormone [FSH], 17ß estradiol), or if of child-bearing potential be on adequate non-hormonal contraception (not oral or injectable) i.e. double barrier method or intrauterine contraceptive device [IUCD]. If male must also use adequate contraception (hormonal methods permitted) 5. Anti-muscarinic-naïve or treated subjects completing the 5 day wash-out period 6. Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. If female, has a positive urine pregnancy test 2. History of drug or alcohol abuse 3. Use of anti-muscarinic agents with a long-half life e.g. solifenacin 4. Body Mass Index (BMI) greater than 28 or less than 16 5. Mean sitting BP greater than 150/85 or less than 100/60mmHg 6. Mean HR greater than 90 bpm or less than 50 bpm 7. Clinically significant orthostatic hypotension present at screening 8. History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or lightheadedness 9. History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, atrial tachycardia, or congestive heart failure 10. History of significant central nervous system disease, including: transient ischemic attack, stroke, seizure disorder, depression, or behavioral disturbances 11. History of peripheral vascular or cerebrovascular disease 12. History of narrow angle glaucoma or increased ocular pressure 13. Clinically significant bladder pathology, including urinary tract infection within 6 weeks of Day 0 14. History of diabetes 15. Clinically significant GI disorder which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study 16. History of clinically significant liver disease, e.g., hepatitis B 17. Prohibited medications taken within 2 weeks 18. Concomitant use of any agent that has a significant interaction with CYP3A4 or P glycoprotein (Pgp) 19. Clinically significant abnormalities in laboratory test results at screening (including hepatic and renal, full blood count, biochemistry and urinalysis) 20. Participation in an investigational drug or device study within 30 days prior to study 21. Known hypersensitivity to anticholinergic agents 22. Concomitant disease or condition which could interfere with, or for which the treatment of might interfere with, the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study. This would include, but is not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease 23. Unwillingness or inability to comply with the study protocol for any other reason 24. Any clinically significant abnormality on 12-lead ECG.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the effects of single oral doses of PSD506 anti-muscarinic antagonist (PSD506) on the reduction of unstable urinary bladder detrusor contractions induced by volume provocation testing in patients with hyper-reflexia secondary to spinal injury. ; Secondary Objective: • To assess the safety of PSD06 in this population • To determine the dose-response of different doses of PSD506 on the reduction of unstable urinary bladder detrusor contractions ; Primary end point(s): Efficacy: The primary efficacy parameter will be the change from baseline to post-dose in the AUC detrusor pressure curve during the volume provocation test. The mean of the AUC from the three repetitions of the VPT will be used. The secondary efficacy parameters will be change from baseline to post-dose in the peak detrusor pressure during the volume provocation test. The mean of the peak detrusor pressure from three repetitions of the VPT will be used. Safety: Adverse events ECG/ Cardiac monitoring • Change in heart rate from baseline • Change in QTc interval from baseline Anti- muscarinic side effects Vital signs Pharmacokinetics: Limited PK samples (baseline and hourly 1 – 3 hours post-dose) will be taken to determine concordance with previously defined profiles in healthy volunteers | — |
Countries
United Kingdom
Outcome results
None listed